Polymers in Medicine

Polim. Med.
Scopus CiteScore: 3.5 (CiteScore Tracker 3.6)
Index Copernicus (ICV 2023) – 121.14
MEiN – 70
ISSN 0370-0747 (print)
ISSN 2451-2699 (online) 
Periodicity – biannual

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Polymers in Medicine

2012, vol. 42, nr 1, January-March, p. 5–16

Publication type: review article

Language: Polish

Polimery jako substancje pomocnicze stosowane w technologii tabletek powlekanych zawierających pochodne kwasu ibandronowego (bisfosfoniany)

Polymers as excipients used in the technology of coated tablets containing ibandronic acid derivatives (bisphosphonates)

Michał Krzysztof Kołodziejczyk1,, Marian Mikołaj Zgoda1,

1 Zakład Technologii Postaci Leku, Katedra Farmacji Stosowanej, Uniwersytet Medyczny w Łodzi

Streszczenie

Bisfosfoniany stosuje się w leczeniu osteoporozy, najczęściej pomenopauzalnej i posteroidowej. Najbardziej znanymi pochodnymi bisfosfonianów są m. in. pochodne kwasu alendronowego, klodronowego, ibandronowego i rizedronowego. Bisfosfoniany posiadają niską biodostępność (1–10%) i niską wchłanialność (dla nowszych bisfosfonianów nie przekracza 1%) po podaniu doustnym (III klasa BCS). Omawiana grupa pochodnych to także wyzwanie technologiczne, szczególnie w sytuacji tak trudnych uwarunkowań biofarmaceutycznych. Powyższe skłania do przestrzegania dyscypliny przyjmowania stałych doustnych postaci farmaceutycznych (tabletki), które muszą być bezwzględnie przyjmowane na czczo (30–60 minut przed posiłkiem) i popijane szklanką przegotowanej wody. Technologia doustnych postaci leku z bisfosfonianami, praktycznie musi do zera minimalizować problemy potencjalnej adsorpcji substancji aktywnej na substancjach pomocniczych o charakterze polimerów wielkocząsteczkowych, wchodzących w skład rdzenia i otoczki tabletek, przy jednoczesnym zapewnieniu pełnej dostępności farmaceutycznej.

Abstract

Bisphosphonates are used in the treatment of osteoporosis, predominantly most often postmenopausal and glucocorticoidinduced forms. The most commonly known bisphosphonates are: derivatives of alendronic, clodronic, ibandronic, risedronic acid. Bisphosphonates have low bioavailability (1–10%) and low absorption (for more recent bisphosphonates it does not exceed 1%) after oral application (class III of BCS). The discussed group of derivatives is also a technological challenge, particularly in a situation of so difficult biopharmaceutical conditions. The above encourages compliance with the discipline of taking solid oral pharmaceutical forms (tablets), which have to be taken strictly on an empty stomach (30–60 minutes before a meal) and washed down with a glass of boiled water. The technology of oral drug forms with bisphosphonates has to minimize practically to zero the problems of potential adsorption of an active substance on excipients of a character of macromolecular polymers being part of a tablet core and a coating, at the same time providing full pharmaceutical availability

Słowa kluczowe

naturalne biopolimery, wielkocząsteczkowe polimery błonotwórcze, bisfosfoniany, kwas ibandronowy, tabletka powlekana, laktoza, rdzeń tabletki powlekanej, skrobia

Key words

natural biopolymers, film forming macromolecular polymers, bisphosphonates, ibandronic acid, coated tablet, lactose, coated tablet core, starch

References (79)

  1. Winzenberg T., Jones G.: When do bisphosphonates make the most sense? J. Fam. Pract. (2011) Jan, 60, (1), 18–28.
  2. Zhou Q., Zhao Z. N., Cheng J. T., Zhang B., Xu J., Huang F., Zhao R. N., Chen Y. J.: Ibandronate promotes osteogenic differentiation of periodontal ligament stemcells by regulating the expression of microRNAs, Biochem. Biophys. Res. Commun. (2011), 404, (1), 127–132.
  3. Kastelan D., Vlak T., Lozo P., Gradiser M., Mijic S., Nikolic T., Miskic B., Car D., Tajsic G., Dusek T., Jajic Z., Grubisic F., Poljicanin T., Bakula M., Dzubur F., Strizak-Ujevic M., Kadojic M., Radman M., Vugrinec M., Kuster Z., Pekez M., Radovic E., Labar L., Crncevic-Orlic Z., Korsic M.: Health-related quality of life among patients with postmenopausal osteoporosis treated with weekly and monthly bisphosphonates. Endocr. Res. (2010), 35, (4), 165–173.
  4. Von Moos R., Caspar C b., Steiner R., Angst R., Inauen R., Schmieding K., Thürlimann B.: Long-term renal safety profile of ibandronate 6 mg infused over 15 Minutes. Onkologie. (2010), 33 (8–9), 447–450.
  5. Miller P. D., Delmas P. D., Huss H., Patel K. M., Schimmer R. C., Adami S., Recker R. R.: Increases in hip and spine bone mineral density are predictive for vertebral antifracture efficacy with ibandronate. Calcif. Tissue Int. (2010), Oct, 87,(4), 305–313.
  6. Epplen R., Stöckle M., Engelmann U., Heidenreich A., Ohlmann C. H.: Differential effects of ibandronate, docetaxel and farnesol treatment alone and in combination on the growth of prostate cancer cell lines. Acta Oncol. 2011 Jan; 50, (1), 127– 133. Epub 2010 Apr 29.
  7. Lolli M. L, Rolando B., Tosco P., Chaurasia S., Di Stilo A., Lazzarato L., Gorassini E., Ferracini R., Oliaro-Bosso S., Fruttero R., Gasco A.: Synthesis and preliminary pharmacological characterisation of a new class of nitrogen-containing bisphosphonates (N-BPs). Bioorg. Med. Chem. (2010), 18 (7), 2428–2438.
  8. Hochberg M. C., Silverman S. L., Barr C. E., Miller P. D.: The utility of changes in serum levels of C-terminal telopeptide of type I collagen in predicting patient response to oral monthly ibandronate therapy. J. Clin. Densitom, (2010), 13,(2), 181–19.
  9. Meattini I., Bruni A., Scotti V., Livi L., De Luca Cardillo C., Galardi A., Cipressi S., Biti G.: Oral ibandronate in metastatic bone breast cancer: the Florence University experience and a review of the literature. J. Chemother. (2010), 22 (1), 58–62.
  10. Jahnke W., Henry C.: An in vitro assay to measure targeted drug delivery to bone mineral. Chem. Med. Chem. (2010), 5, (5), 770–776.
  11. Orwoll E. S., Binkley N. C., Lewiecki E. M., Gruntmanis U., Fries M. A., Dasic G.: Efficacy and safety of monthly ibandronate in men with low bone density, Bone, (2010), 46, (4), 970–976.
  12. Bunyaratavej N., Wajanavisit W., Pauvilai P., Kitumnuoypong T., Kittimanon N., Lektrakoon S.: Safety and antisorptive power of Ibandronate applied in the real-life setting. J. Med. Assoc. Thai., (2009), 92, Suppl5, 72–75.
  13. Derman R., Kohles J. D., Babbitt A.: Gastrointestinal tolerability with ibandronate after previous weekly bisphosphonate treatment. Clin. Interv. Aging., (2009), 4, 357–365.
  14. Epstein S, Jeglitsch M, Mccloskey E.: Update on monthly oral bisphosphonate therapy for the treatment of osteoporosis: focus on ibandronate 150 mg and risedronate 150 mg. Curr. Med. Res. Opin., (2009), 25 (12), 2951–2960.
  15. Henrich D. M., Hoffmann M., Uppenkamp M., Bergner R.: Tolerability of dose escalation of ibandronate in patients with multiple myeloma and end-stage renal disease: a case series. Onkologie, (2009), 32, (8–9), 482–486.
  16. Bivi N., Romanello M., Harrison R., Clarke I., Hoyle D. C., Moro L., Ortolani F., Bonetti A., Quadrifoglio F., Tell G., Delneri D.: Identification of secondary targets of N-containing bisphosphonates in mammalian cells via parallel competition analysis of the barcoded yeast deletion collection. Genome. Biol. (2009), 10, (9), 93.
  17. Amling M., Kurth A.: Ibandronate: a review of its vertebral and nonvertebral antifracture efficacy. Womens Health (Lond. Engl.), (2009), 5, (5), 467–473.
  18. Rossini M., Viapiana O., Gatti D., Adami S.: Once-monthly oral ibandronate in postmenopausal osteoporosis: translation and updated review. Clin. Ther. (2009), 31, (7), 1497–1510.
  19. Lakatos P.: Ibandronate in the treatment of postmenopausal osteoporosis. Lege Artis Med., (2008), 18, (10), 657–661.
  20. Bilezikian J. P.: Efficacy of bisphosphonates in reducing fracture risk in postmenopausal osteoporosis. Am. J. Med. (2009), 122, (2 Suppl.), 14–21.
  21. Binkley N., Silverman S. L, Simonelli C., Santiago N., Kohles J. D., Dasic G., Sunyecz J. A.: Monthly ibandronate suppresses serum CTX-I within 3 days and maintains a monthly fluctuating pattern of suppression. Osteoporos Int. (2009), 20, (9), 1595–1601.
  22. Reginster J. Y., Neuprez A., Bruyère O.: Ibandronate in profile: drug characteristics and clinical efficacy. Expert Opin. Drug. Meta.b Toxicol., (2008), 4, (7), 941–951.
  23. Joensuu T. K.: Renal toxicity following zoledronic acid reversed with ibandronate in a prostate cancer patient with bone metastases. Urol. Int. (2008), 80, (4), 448–450.
  24. Mystakidou K., Stathopoulou E., Parpa E., Kouloulias V., Kouskouni E., Vlahos L.: Oral versus intravenous ibandronic acid: a comparison of treatment options for metastatic bone disease. J. Cancer Res. Clin. Oncol., (2008), 134, (12), 1303– 1310.
  25. [No authors listed]: Ibandronic acid: new drug. Osteoporosis: one tablet a month, but risk of a “flu-like” syndrome. Prescrire Int. (2008), 17, (93), 11.
  26. Kreck S., Klaus J., Leidl R., Von Tirpitz C., Konnopka A., Matschinger H., König H. H.: Cost effectiveness of ibandronate for the prevention of fractures in inflammatory bowel disease-related osteoporosis: cost-utility analysis using a Markov model. Pharmacoeconomics, (2008), 26, (4), 311–328.
  27. Kastelan D., Vlak T.: Does ibandronate (Bonviva) have an impact on non-vertebral fractures? Reumatizam.(200)7, 54, (2), 87–88.
  28. Jansen J. P., Gaugris S., Bergman G., Sen S. S.: Cost-effectiveness of a fixed dose combination of alendronate and cholecalciferolin the treatment and prevention of osteoporosis in the United Kingdom and The Netherlands. Curr. Med. Res. Opin., (2008), 24, (3), 671–684.
  29. Miller P. D., Epstein S., Sedarati F., Reginster J. Y.: Once-monthly oral ibandronate compared with weekly oral alendronate in postmenopausal osteoporosis: results from the head-to-head Motion study. Curr. Med. Res. Opin. (2008), 24, (1), 207–213.
  30. Gold D. T., Safi W., Trinh H.: Patient preference and adherence: comparative US studies between two bisphosphonates, weekly risedronate and monthly ibandronate. Curr. Med. Res. Opin. (2006), 22, (12), 2383–2391.
  31. Kessenich C. R.: Ibandronate (boniva) offers new options for osteoporosis. Nurse Pract., (2006), 31, (10), 64–66.
  32. Pyon E. Y.: Once-monthly ibandronate for postmenopausal osteoporosis: review of a new dosing regimen. Clin. Ther., (2006), 28, (4), 475–490.
  33. Dempster D. W., Bolognese M. A.: Ibandronate: the evolution of a once-a-month oral therapy for postmenopausal osteoporosis. J. Clin. Densitom., (2006), 9, (1), 58–65.
  34. Mccormack P. L., Plosker G. L.: Ibandronic acid: a review of its use in the treatment of bone metastases of breast cancer. Drugs. (2006), 66, (5), 711–728.
  35. Epstein S.: Ibandronate treatment for osteoporosis: rationale, preclinical, and clinical development of extended dosing regimens. Curr. Osteoporos. Rep. (2006), 4, (1), 14–20.
  36. Cooper C.: Beyond daily dosing: clinical experience. Bone, (2006), 38, (4 Suppl 1), 13–17.
  37. Polk B.: Ibandronate once a month. Med. Monatsschr. Pharm. (2006), 29, (1), 36–37.
  38. Emkey R., Koltun W., Beusterien K., Seidman L., Kivitz A., Devas V., Masanauskaite D.: Patient preference for oncemonthly ibandronate versus once-weekly alendronate in a randomized, open-label, cross-over trial: the Boniva Alendronate Trial in Osteoporosis (BALTO), Curr. Med. Res. Opin. (2005), 21, (12), 1895–1903.
  39. Reginster J. Y., Adami S., Lakatos P., Greenwald M., Stepan J. J., Silverman S. L.,Christiansen C., Rowell L., Mairon N., Bonvoisin B., Drezner M. K., Emkey R., Felsenberg D., Cooper C., Delmas P. D., Miller P. D.: Efficacy and tolerability of once-monthly oral ibandronate in postmenopausal osteoporosis: 2 year results from the MOBILE study. Ann. Rheum. Dis. (2006), 65, (5), 654–661.
  40. Dando T. M., Noble S.: Once-monthly ibandronate, Treat. Endocrinol., (2005), 4, (6), 381–387, discussion 389–390.
  41. Reginster J. Y, Felsenberg D., Cooper C., Stakkestad J. A., Miller P. D., Kendler D. L., Adami S., Mcclung M. R., Bolognese M. A., Civitelli R., Dumont E., Bonvoisin B., Recker R. R., Delmas P. D.: A new concept for bisphosphonate therapy: a rationale for the development of monthly oral dosing of ibandronate. Osteoporos Int. (2006), 17,(2), 159–166.
  42. Kim H. K., Randall T. S., Bian H., Jenkins J., Garces A., Bauss F.: Ibandronate for prevention of femoral head deformity after ischemic necrosis of the capital femoral epiphysis in immature pigs J. Bone. Joint Surg. Am. (2005) Mar, 87, (3), 550–557.
  43. Gennari L.: Oral ibandronic acid. I D rugs, (2005), Feb, 8, (2), 155–169.
  44. Body J. J., Diel I. J., Bell R., Pecherstorfer M., Lichinitser M. R., Lazarev A. F., Tripathy D., Bergström B.: Oral ibandronate improves bone pain and preserves quality of life in patients with skeletal metastases due to breast cancer. Pain., (2004), 111, (3), 306–312.
  45. Barrett J., Worth E., Bauss F., Epstein S.: Ibandronate: a clinical pharmacological and pharmacokinetic update. J. Clin. Pharmacol. (2004), 44, (9), 951–965.
  46. Body J. J., Diel I. J., Lichinitzer M., Lazarev A., Pecherstorfer M., Bell R., Tripathy D., Bergstrom B.: Oral ibandronate reduces the risk of skeletal complications in breast cancer patients with metastatic bone disease: results from two randomised, placebo-controlled phase III studies. Br. J. Cancer. (2004), 90, (6), 1133–1137.
  47. Cooper C., Emkey R. D., Mcdonald R. H., Hawker G., Bianchi G., Wilson K., Schimmer R. C.: Efficacy and safety of oral weekly ibandronate in the treatment of postmenopausal osteoporosis. J. Clin. Endocrinol. Metab., (2003), 88, (10), 4609–4615.
  48. Stepan J. J., Burckhardt P., Hána V.: The effects of three-month intravenous ibandronate on bone mineral density and bone remodeling in Klinefelter’s syndrome: the influence of vitamin D deficiency and hormonal status. Bone., (2003), 33, (4), 589–596.
  49. Heidenreich A., Elert A., Hofmann R.: Ibandronate in the treatment of prostate cancer associated painful osseous metastases. Prostate Cancer Prostatic Dis. (2002), 5,(3), 231–235.
  50. Riis B. J., Ise J., Von Stein T., Bagger Y., Christiansen C.: Ibandronate: a comparison of oral daily dosing versus intermittent dosing in postmenopausal osteoporosis. J. Bone Miner. Res. (20010, 16, (10), 1871–1878.
  51. Fisher J. E., Rodan G. A., Reszka A. A.: In vivo effects of bisphosphonates on the osteoclast mevalonate pathway. Endocrinology, (2000), 141, (12), 4793–4796.
  52. Cruz J. C., Alsina M., Craig F., Yoneda T., Anderson J. L., Dallas M., Roodman G. D.: Ibandronate decreases bone disease development and osteoclast stimulatory activity in an in vivo model of human myeloma. Exp. Hematol. 2001, 29(4), 441–447.
  53. Richards P. J., Amos N., Williams A. S., Williams B. D.: Pro-inflammatory effects of the aminobisphosphonate ibandronate in vitro and in vivo. Rheumatology (Oxford). (1999), 38, (10), 984–991.
  54. Dooley M., Balfour J. A.: Ibandronate. Drugs, (1999), 57, (1), 101–108; discussion 109–110.
  55. Burckhardt P.: Ibandronate in oncology. Cancer. (1997), 15, 80, (8 Suppl), 1696–1698.
  56. Yoneda T., Sasaki A., Dunstan C., Williams P. J., Bauss F., De Clerck Y. A., Mundy G. R.: Inhibition of osteolytic bone metastasis of breast cancer by combined treatment with the bisphosphonate ibandronate and tissue inhibitor of the matrix metalloproteinase-2. J. Clin. Invest. (1997), 15, 99, (10), 2509–2517.
  57. Antic V. N., Fleisch H., Mühlbauer R. C.: Effect of bisphosphonates on the increase in bone resorption induced by a low calcium diet. Calcif. Tissue Int. (1996), 58, (6), 443–448.
  58. Wnuk R. S., Kokot F., Więcek A., Irzyniec T.: Use of third generation bisphosphonates in treatment of neoplastic hypercalcemia. Pol. Tyg. Lek. (1995), 50, (44–47), 43–44.
  59. Monier-Faugere M. C., Friedler R. M, Bauss F., Malluche H. H.: A new bisphosphonate, BM 21.0955, prevents bone loss associated with cessation of ovarian function in experimental dogs. J. Bone Miner. Res., (1993), 8, (11), 1345–1355.
  60. Wüster C., Schöter K. H., Thiébaud D., Manegold C., Krahl D., Clemens M.R., Ghielmini M., Jaeger P., Scharla H.: Methylpentylaminopropylidenebisphosphonate (BM 21.0955): a new potent and safe bisphosphonate for the treatment of cancerassociated hypercalcemia. Bone Miner. (1993), 22, (2), 77–85.
  61. Mühlbauer R. C., Bauss F., Schenk R., Janner M., Bosies E., Strein K., Fleisch H.: BM 21.0955, a potent new bisphosphonate to inhibit bone resorption. J. Bone. Miner. Res. (1991), 6, (9),1003–1011.
  62. Zgoda M. M.: Aktualnie stosowane substancje pomocnicze w technologii stałych doustnych środków farmaceutycznych. Farm. Pol., (2003), 59, 19, 890–897.
  63. Kotagale N., Maniyar M., Somvanshi S., Umekar M., Patel C. J.: Eudragit-S, Eudragit-L and cellulose acetate phthalate coated polysaccharide tablets for colonic targeted delivery of azathioprine. Pharm. Dev. Technol., (2010), 5, (4), 431–437.
  64. Zgoda M. M., Nachajski M. J., Kołodziejczyk M. K.: Microcrystalline cellulose and their flow morphological properties modifications as an effective excpients in tablet formulation technology containing lattice established API and also dry plant extract. Polim. Med. (2009), 39, (1), 17–30.
  65. Shi L., Feng Y., Sun C. C.: Roles of granule size in over-granulation during high shear wet granulation J. Pharm. Sci. (2010), 99, (8), 3322–3325.
  66. Badawy S. I., Shah K. R., Surapaneni M. S., Szemraj M. M., Hussain M.: Effect of spray-dried mannitol on the performance of microcrystalline cellulose-based wet granulated tablet formulation. Pharm. Dev. Technol., (2010), 15, (4), 339–345.
  67. Muschert S., Siepmann F., Leclercq B., Carlin B., Siepmann J.: Drug release mechanisms from ethylcellulose: PVA-PEG graft copolymer-coated pellets. Eur. J. Pharm. Biopharm., (2009), 72, (1), 130–137.
  68. Schmid W., Picker-Freyer K. M.: Tableting and tablet properties of alginates: characterisation and potential for Soft Tableting. Eur. J. Pharm. Biopharm., (2009), 72, (1), 165–172.
  69. Nagato L. K., Lourenço M. G., Cadete R. A., Leite-Júnior J. H., Koatz V. L., Rocco P. R., Faffe D. S., Zin W.A.: Microcrystalline cellulose induces time-dependent lung functional and inflammatory changes. Respir. Physiol. Neurobiol. (2008), 31, 164, (3), 331–337.
  70. Sankalia J. M., Sankalia M. G., Mashru R. C.: Drug release and swelling kinetics of directly compressed glipizide sustainedrelease matrices: establishment of level A IVIVC. J. Control Release, 9), 129, (1), 49–58.
  71. Zgoda M. M., Nachajski M. J., Kołodziejczyk M. K., Woskowicz M. H., Lukosek M.: Solubilizing and lithogenolitic properties of water solutions of non-ionic surfactants of cholesterol oxyethylenation products. Polim. Med. (2007), 37, (4), 39–57.
  72. Hauschild K., Picker-Freyer K. M.: Evaluation of tableting and tablet properties of Kollidon SR: the influence of moisture and mixtures with theophylline monohydrate. Pharm. Dev. Technol. (2006), 11, (1), 125–140.
  73. Zgoda M. M., Kolodziejczyk M. K., Nachajski M. J.: Starch and its derivatives as excipients in oral and parenteral drug form technology, Polim. Med. 2009, 39(1), 31–45.
  74. Huang Y.B., Tsai Y. H., Yang W. C., Chang J. S., Wu P. C., Takayama K.: Oncedaily propranolol extended-release tablet dosage form: formulation design and in vitro/in vivo investigation. Eur. J. Pharm. Biopharm., (2004), 58, (3), 607–614.
  75. Westermarck S., Juppo A. M., Kervinen L., Yliruusi J.: Microcrystalline cellulose and its microstructure in pharmaceutical processing. Eur. J. Pharm. Biopharm. (1999), 48, (3), 199–206.
  76. Nicolas V., Chambin O., Andrès C., Rochat-Gonthier M. H., Pourcelot Y.: Preformulation: effect of moisture content on microcrystalline cellulose (Avicel PH-302) and its consequences on packing performances. Drug Dev. Ind. Pharm. (1999), 25, (10), 1137–1142.
  77. Suzuki T., Nakagami H.: Effect of crystallinity of microcrystalline cellulose on the compactability and dissolution of tablets. Eur. J. Pharm. Biopharm. (1999), 47, (3), 225–230.
  78. Zgoda M. M., Nachajski M. J., Kołodziejczyk M. K., Woskowicz M. H., Lukosek M.: Solubilizing properties of new surfaceactive agents, products of selective oxyethylation of cholic acid. Part I. Polim. Med. (2007), 37, (4), 21–38.
  79. Kołodziejczyk M. J., Nachajski M. J., Kołodziejczyk M. K.: Prediction the technological parameters of a merket pharmaceutical product based on list of excipients proposed by the manufacturer. Milit. Pharm. and Med., (2009), 2, (1–2), 264–270.
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